异动症大鼠直接通路中DARPP-32蛋白变化的机制  

Mechanism of the change of DARPP-32 in over-activation of direct-pathway in rats with levodopa-induced dyskinesias

作　　者：梁直厚[1] 管强[1] 曹学兵[1] 徐岩[1] 王岚[1] 孙圣刚[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院神经科,武汉430022

出　　处：《中国康复医学杂志》2006年第11期963-966,共4页Chinese Journal of Rehabilitation Medicine

基　　金：国家自然科学基金资助项目(30300114)

摘　　要：目的:观察左旋多巴诱发异动症(LID)大鼠模型行为学特点及DARPP-32蛋白的磷酸化状态的变化,探讨LID的发生机制。方法:复制成功的帕金森病(Parkinson′sdisease,PD)大鼠应用左旋多巴治疗28d诱发LID大鼠模型,进行异常不自主运动(abnormalinvoluntarymovement,AIM)评分,并采用逆转录聚合酶链式反应及免疫印迹技术检测LID大鼠纹状体内总DARPP-32的mRNA与蛋白表达及其Thr-34位点磷酸化水平。结果:LID大鼠模型复制成功后出现了与人类LID相似的对侧前肢、躯干和口面部AIM,并随左旋多巴治疗时间的延长而加重。LID大鼠Thr-34位点磷酸化的DARPP-32水平较对照组及左旋多巴治疗组明显增高,差异均有显著性意义(P<0.01)。结论:长期间断性给PD大鼠左旋多巴能复制出LID大鼠模型,DARPP-32的Thr-34位点的磷酸化水平的改变是LID时多巴胺D1受体介导的直接通路异常活化的关键因素之一。Objective：To study the character of behavior and change of dopamine and cAMP-regulated phosphoprotein（DARPP-32） phosphorylation expression in order to explore the mechanism in rats with levodopa-induced dyskinesias.Metbod： Parkinson disease（PD） rats received levodopa（10 mg/kg） celiac injections twice daily for 28 days to get the LID model rats. Normal rats received the same course and dosage of levodopa as a control group. Behavior changes of rats were assessed. Protein expression and mRNA levels of total DARPP-32 and phospho-Thr-34 DARPP-32 level in rat＇s striatum were measured by immunoblotting and reverse transcriptase-polymerase chain reaction （RT-PCR）,respectively.Result： Prolonged intermittent treatment with levodopa induced contralateral forelimb, trunk and orofacial abnormal involuntary movement （AIM） in PD rats,similar to LID in PD patients. The levels of PDyn mRNA and phospho-Thr-34 DARPP-32 both increased significantly in LID rats compared to control and levodopa treatment rats（P〈0.01）. Conclusion：LID model in rats could be established by prolonged intermittent treatment with levodopa to PD rats. Phospho-Thr-34 DARPP-32 level was increased in LID rats,which contribute to the over-activation in direct-pathway.

关 键 词：左旋多巴 异动症 DARPP-32蛋白 帕金森病 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R595.3[医药卫生—临床医学]